Protocol The remote diet intervention to reduce Long COVID symptoms trial (ReDIRECT) [...], 2023, Haag et al

[forestglip]

Now published - link here
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The remote diet intervention to reduce Long COVID symptoms trial (ReDIRECT): protocol for a randomised controlled trial to determine the effectiveness and cost-effectiveness of a remotely delivered supported weight management programme for people with Long COVID and excess weight, with personalised improvement goals

Laura Haag, Janice Richardson, Yvonne Cunningham, Heather Fraser, Naomi Brosnahan, Tracy Ibbotson, Jane Ormerod, Chris White, Emma McIntosh, Kate O'Donnell, Naveed Sattar, Alex McConnachie, Michael E J Lean, David N Blane, Emilie Combet

Abstract

Objectives:
The Remote Diet Intervention to Reduce Long COVID Symptoms Trial (ReDIRECT) evaluates whether the digitally delivered, evidence-based, cost-effective Counterweight-Plus weight management programme improves symptoms of Long COVID in people with overweight/obesity.

Methods:
Baseline randomised, non-blinded design with 240 participants allocated in a 1:1 ratio either to continue usual care or to add the remotely delivered Counterweight-Plus weight management programme, which includes a Counterweight dietitian supported delivery of 12 weeks total diet replacement, food reintroduction, and long-term weight loss maintenance. Randomisation is achieved by accessing a web-based randomisation system incorporated into the study web portal developed by a registered Clinical Trials Unit. We are using an innovative approach to outcome personalisation, with each participant selecting their most dominant Long COVID symptom as their primary outcome assessed at six months. Participants in the control arm enter the weight management programme after six months. We are recruiting participants from social media and existing networks (e.g., Long COVID Scotland groups), through newspaper advertisements and from primary care. Main inclusion criteria: people with Long COVID symptoms persisting > three months, aged 18 years or above, body mass index (BMI) above 27kg/m 2 (>25kg/m 2 for South Asians). The trial includes a process evaluation (involving qualitative interviews with participants and analysis of data on dose, fidelity and reach of the intervention) and economic evaluation (within-trial and long-term cost-utility analyses).

Anticipated results:
The recruitment for this study started in December 2021 and ended in July 2022. Project results are not yet available and will be shared via peer-reviewed publication once the six-months outcomes have been analysed.



Plain language summary
While most people infected with COVID-19 recover within a short amount of time, some people continue to have symptoms for 12 weeks or longer. This condition is known as Long COVID. Roughly two-thirds of people with Long COVID are overweight, a proportion similar to that found in the general population. Being overweight may worsen symptoms such as fatigue, breathlessness and pains. Weight management programmes in adults with overweight/obesity can reduce such symptoms, however we do not know how effective intentional weight loss is to reduce symptoms for people with Long COVID. The aim of this project is to test a well-established weight management programme, delivered and supported remotely, in people with Long COVID.

The trial is conducted with 240 people with Long COVID, identified through their GP, patient groups, social media, or newspaper advertisements. A total of 120 individuals will receive the personalised, professionally supported weight management programme (treatment group), and 120 participants are allocated to usual care (control group). The one-year long weight management programme involves 12 weeks of total diet replacement (TDR) using soups and shakes, followed by food reintroduction and weight maintenance. Food based alternatives are available to those who are unable, or prefer not to, follow the TDR approach. The two groups will be compared for Long COVID symptoms, weight loss, quality of life and value for money after six months. After six months, the weight management programme will also be provided for the control group. Experiences while on the programme will be documented for 12 months for all participants.

People with Long COVID have been involved extensively in developing this project. Their priorities are to reduce symptoms like fatigue, breathlessness and pain. They are keen to explore if effective weight management would help their symptoms and overall functioning, especially a programme that can be followed remotely from home. A group of patients and other stakeholders has been set up to provide advice throughout the project.

Conflict of interest statement
Competing interests: AM is a member of Clinical Steering Committee for ARC Medical Inc. NS has received institutional grant support from AstraZeneca, Boehringer Ingelheim, Novartis, Roche Diagnostics and honoraria from Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Sanofi ML has consulted for Novo Nordisk, Nestle, Oviva, Merck, Sanofi and is an unpaid medical advisor to Counterweight Ltd. NB is an employee and shareholder of Counterweight Ltd., subcontracted to the University of Glasgow to deliver the ReDIRECT intervention

Full text (PubMed Central) | Trial registration

 

[forestglip]

Registration page says the study ended on 31 May 2024, and they intend to publish on 1 November 2024.

 

[forestglip]

Previous trial studying this intervention in diabetes:

Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial, 2017, Lean et al

we recruited 306 individuals from 49 intervention (n=23) and control (n=26) general practices; 149 participants per group comprised the intention-to-treat population.

We recruited individuals aged 20–65 years who had been diagnosed with type 2 diabetes within the past 6 years, had a body-mass index of 27–45 kg/m2, and were not receiving insulin. The intervention comprised withdrawal of antidiabetic and antihypertensive drugs, total diet replacement (825–853 kcal/day formula diet for 3–5 months), stepped food reintroduction (2–8 weeks), and structured support for long-term weight loss maintenance. Co-primary outcomes were weight loss of 15 kg or more, and remission of diabetes, defined as glycated haemoglobin (HbA1c) of less than 6·5% (<48 mmol/mol) after at least 2 months off all antidiabetic medications, from baseline to 12 months.

At 12 months, we recorded weight loss of 15 kg or more in 36 (24%) participants in the intervention group and no participants in the control group (p<0·0001). Diabetes remission was achieved in 68 (46%) participants in the intervention group and six (4%) participants in the control group (odds ratio 19·7, 95% CI 7·8–49·8; p<0·0001). Remission varied with weight loss in the whole study population, with achievement in none of 76 participants who gained weight, six (7%) of 89 participants who maintained 0–5 kg weight loss, 19 (34%) of 56 participants with 5–10 kg loss, 16 (57%) of 28 participants with 10–15 kg loss, and 31 (86%) of 36 participants who lost 15 kg or more.

Link (The Lancet) [Paywall]

 

[tornandfrayed]

Hmm -

While most people infected with COVID-19 recover within a short amount of time, some people continue to have symptoms for 12 weeks or longer. This condition is known as Long COVID. Roughly two-thirds of people with Long COVID are overweight, a proportion similar to that found in the general population. Being overweight may worsen symptoms such as fatigue, breathlessness and pains. Weight management programmes in adults with overweight/obesity can reduce such symptoms, however we do not know how effective intentional weight loss is to reduce symptoms for people with Long COVID. The aim of this project is to test a well-established weight management programme, delivered and supported remotely, in people with Long COVID.

So, rate of being overweight is the same as the general population.

Losing weight may help some non-ME LC sufferers but this isn't a healthy diet. Surely meal replacements are the epitome of ultra-processed foods, about which there's much concern. Also replacing a normal diet in this way doesn't help people to learn healthy eating patterns.

No mention of pwLC struggling to buy and prepare food, difficulties with digestion, new food intolerances or allergies.

 

[forestglip]

Losing weight may help some non-ME LC sufferers but this isn't a healthy diet. Surely meal replacements are the epitome of ultra-processed foods, about which there's much concern. Also replacing a normal diet in this way doesn't help people to learn healthy eating patterns.

The meal replacement stage is only the first 8-12 weeks, then a 4-12 week transition into a full-food diet, which will be eaten the rest of the six months (~0-12 weeks). A counselor will help them maintain a healthy diet. And outcomes will be measured at 12 months.

The format and support of the intervention is delivered remotely by the evidence-based Counterweight-Plus Programme ( Lean et al., 2018). All support is delivered by registered dietitians. Counterweight-Plus is a structured intervention utilising total diet replacement (TDR), and behaviour change to help people lose at least 15 kg (or 15% of their body weight if over 100 kg) and keep it off long term. Recognising that fatigue and mobility difficulties are frequent among people living with Long COVID and among those living with obesity, the programme is delivered to participants’ homes and supported entirely remotely and patient-reported outcomes are used to maximise acceptability and protocol adherence.

The programme runs for 12 months and is divided into two phases:

Weight loss induction phase (from week 0 to week 8–12)
Counterweight provides 8–12 weeks of a low-energy, nutritionally complete, formula diet (850 kcal/day) to replace all meals (total diet replacement, TDR), aiming for ≥15 kg (or 15% of their body weight if over 100kg) weight loss. Products include a variety of soups and shakes provided free of cost to the participant. Those who are unable, or prefer not to, follow the TDR formula diet (10% in the published DiRECT study ( Lean et al., 2018)) are offered an alternative approach providing 1200 kcal/day, either a meal replacement diet in which a maximum of two meal replacements are consumed per day or a food-based low-carb or low-fat approach. Food used to supplement the TDR or for fully food-based plans is purchased by the participants and not provided by the study. To increase adherence to the programme, support is tailored to individual participants, allowing for flexibility around commitments or life events. Further strategies are pre-emptively discussed, e.g., the possibility of adding in one meal/day or including ‘days off’, with encouragement to resume the full TDR at subsequent visits and to maintain whatever weight has already been lost and moving onto the maintenance phase early if necessary to avoid dropping out altogether.

Weight loss maintenance phase (week 8/12 – six months)
Food is reintroduced stepwise while reducing TDR. The transition period to a full food-based diet lasts between 4–12 weeks (usually eight weeks) and is individualised to participants. A management plan will be provided along with support for standard evidence-based behaviour change techniques, including self-monitoring of behaviours and behavioural outcomes, goal-setting and self-rewards, action planning, and problem solving. During this time, participants measure their weight weekly and enter this into the Counterweight App to monitor progress with weight loss maintenance.

Relapse treatments are available for >2 kg weight gain. These include reinforcing behaviour change techniques and the option to return to TDR, a 1,200-kcal meal replacement diet, or a 1,200-kcal low carb or low-fat diet for two weeks. Alternative evidence-based dietary strategies are considered on an individual basis (intermittent or alternate-day fasting, time-restricted eating).

Counterweight dietitians provide personalised support throughout the 12-month intervention via text chat, video or telephone, in-app weekly monitoring, nudges, and personalised messaging. Remote appointments are offered on a monthly basis, following initiation into the programme, however, these appointments are flexible to the needs of individuals.

 

[forestglip]

No mention of pwLC struggling to buy and prepare food

The dominant symptom of Long COVID is fatigue ( Lopez-Leon et al., 2021), which is often an obstacle to engagement with conventional dietary programmes for weight management. Therefore, interventions must suit people whose symptoms impair mobility and ability to attend external appointments. The study design takes potential barriers into consideration in the following ways. First, the Counterweight-Plus weight management programme is known to be effective, safe, nutritionally complete, and is provided by a recognised NHS provider. Second, the entire programme has been adapted for entirely remote delivery (app, online portal, and personalised professional support via text chat, video, or telephone), extending reach, scalability, and removing the burden of out-of-home study visits. Third, the intervention focusses on diet only with no specific requirement for exercise (which may not be appropriate or acceptable for people living with Long COVID) but an individually tailored guidance on being active. Fourth, the diet intervention simplifies meal planning and decision-making, which is particularly helpful for those experiencing difficulties concentrating or fatigue.

 

[Hutan]

It doesn't sound terrible, but the outcome looks to be a subjective one:

We are using an innovative approach to outcome personalisation, with each participant selecting their most dominant Long COVID symptom as their primary outcome assessed at six months.

So, we have the common problem of a subjective outcome in an unblinded study, and confounded by some likely disease-unrelated improvements in wellbeing resulting from weight loss in those participants fortunate enough to achieve it.

No doubt, if you take a sample of overweight people from the general population and support them closely for months in order to help them lose some weight, there will be some reported benefits. But here, that likely benefit will be mixed up with Long Covid, allowing the people marketing the idea and the soups and smoothies to claim benefits in Long Covid.

I can't help, in my cynical way, to think that the study is incredibly well-named. Studies like this redirect attention away from the actual cause of the symptoms and teh actual problem, and instead focus on all the usual 'blame the patient' ideas.

The trial includes a process evaluation (involving qualitative interviews with participants and analysis of data on dose, fidelity and reach of the intervention) and economic evaluation (within-trial and long-term cost-utility analyses).

What's the likely outcome? The company making the shakes gets a contract with the NHS to provide this programme to people with Long Covid, and medical professionals can sign their patient up, with everyone concerned feeling happy that something constructive has been done. Not so great for the patient though, who may or may not lose some weight and may or may not keep it off, but probably, after a while realises that their LC symptoms haven't changed much. ... Apart from the select few patients who do lose weight and do recover, who probably were always going to recover, and become svelte influencers, telling the world how Long Covid can be cured by a bit of will power and some protein shakes.

 

[forestglip]

Paper for the trial has been published (link to thread):

Remotely delivered weight management for people with long COVID and overweight: the randomized wait-list-controlled ReDIRECT trial (2025, Nature Medicine)